This invention relates to coupling reactions of aryl halides with unsaturated silanes, which can be used for chemical synthesis in the polymer and the fine chemical industry.
Metal catalyzed coupling reactions of aryl bromides, aryl iodides, and aryl pseudohalides (e.g., triflates) with various substrates is a general method employed for the formation of Cxe2x80x94C bonds. Prior art methods generally cannot employ aryl chlorides as feedstock for these chemical transformations, and require the use of more expensive aryl bromides and aryl iodides. The use of aryl chlorides as chemical feedstock in coupling chemistry has proven difficult but would economically benefit a number of industrial processes. The few prior art methods that can employ aryl chlorides use expensive, air-sensitive phosphine ligands. In addition, phosphine ligands are often difficult to remove from the process product.
Nucleophilic N-heterocyclic carbenes, the imidazoline-2-ylidenes (sometimes commonly called imidazol-2-ylidenes) or so-called xe2x80x9cphosphine mimicsxe2x80x9d, have attracted considerable attention as possible alternatives for the widely used phosphine ligands in homogeneous catalysis. A primary advantage of these ligands is that an excess of the ligand is not required. It appears that these ligands do not dissociate from the metal center, thus preventing aggregation of the catalyst to yield the bulk metal.
This invention provides a process for conducting coupling reactions of aryl halides with unsaturated silanes. The catalyst system of the present invention permits the use of aryl chlorides as substrates in these coupling reactions while eliminating the need for phosphine ligands. Furthermore, both electron-donating and electron-withdrawing substituents on the aryl halide or pseudohalide, the silane, or both, in the coupling reaction are well tolerated by the catalyst system of the present invention, and provide the corresponding heterocoupled products in excellent yields.
An embodiment of this invention provides a process which comprises mixing, in a liquid medium, i) at least one strong base; ii) at least one aryl halide or aryl pseudohalide in which all substituents are other than silyl groups, wherein the aryl halide has, directly bonded to the aromatic ring(s), at least one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom; iii) at least one silane wherein the silicon atom is quaternary, wherein one group bound to the silicon atom is unsaturated at the alpha or beta position, and wherein each of the remaining groups bound to the silicon atom is a saturated hydrocarbyl or saturated hydrocarbyloxy group; iv) at least one metal compound comprising at least one metal atom selected from nickel, palladium, and platinum, wherein the formal oxidation state of the metal is zero or two; and v) at least one N-heterocyclic carbene. The N-heterocyclic carbene is selected from the group consisting of an imidazoline-2-ylidene wherein at least the 1 or the 3 position is substituted by a secondary or tertiary group which has at least three atoms, or a protonated salt thereof; an imidazolidine-2-ylidene wherein at least the 1 or the 3 position is substituted by a secondary or tertiary group which has at least three atoms, or a protonated salt thereof; a bis(imidazoline-2-ylidene) wherein a bridging moiety is bound to one nitrogen atom of each ring, and wherein the remaining two nitrogen atoms are each, independently, substituted by a secondary or tertiary group which has at least three atoms, or a protonated salt thereof; a bis(imidazolidine-2-ylidene) wherein a bridging moiety is bound to one nitrogen atom of each ring, and wherein the remaining two nitrogen atoms are each, independently, substituted by a secondary or tertiary group which has at least three atoms, or a protonated salt thereof; and mixtures of two or more of the foregoing.
Further embodiments and features of this invention will be apparent from the ensuing description and appended claims.
The liquid medium for the processes of this invention can include any of a wide range of solvents, and mixtures of solvents are also usable. The exclusion of water is not necessary, but is preferred. Types of solvents that can be used include hydrocarbons, ethers, amides, ketones, and alcohols. Polar solvents are preferred; ethers are a more preferred solvent type. Ethers that may be used include, for example, diethyl ether, di-n-propyl ether, diisopropyl ether, tert-butyl ethyl ether, diheptyl ether, 1,3-dioxolane, 1,4-dioxane, tetrahydrofuran, methyltetrahydrofuran, glyme (the dimethyl ether of ethylene glycol), diglyme (the dimethyl ether of diethylene glycol), and the like. Cyclic ethers and polyethers are preferred; a highly preferred ether is 1,4-dioxane.
A variety of strong bases can be used in the processes of this invention. Fluoride salts are a preferred group of bases. Preferable counterions for the fluoride anion are alkali metal cations and ammonium cations. When an alkali metal fluoride is used, it can be lithium fluoride, sodium fluoride, potassium fluoride, rubidium fluoride, or cesium fluoride, and is preferably cesium fluoride. It is more preferable to use an ammonium fluoride. Suitable substituents for the ammonium cation include hydrogen atoms and hydrocarbyl groups, whether straight chain, branched, or-cyclic. Preferred hydrocarbyl substituents have from 1 to about 10 carbon atoms. Examples of ammonium fluoride salts that can be used in this invention include, but are not limited to, ammonium fluoride (NH4F), trimethylammonium fluoride, tetramethylammonium fluoride, phenyltrimethylammonium fluoride, benzyltrimethylammonium fluoride, tetraethylammonium fluoride, tetrapropylammonium fluoride, diisopropylammonium fluoride, isopropylcyclohexylammonium fluoride, tetrabutylammonium fluoride, diisobutylammonium fluoride, cyclopentylammonium fluoride, dicyclohexylammonium fluoride, heptylammonium fluoride, tetraoctylammonium fluoride, dinonylammonium fluoride, n-decylammonium fluoride, and tribenzylammonium fluoride. It is preferred that all four substituents of the ammonium cation are hydrocarbyl groups. Preferred ammonium fluoride salts are tetramethylammonium fluoride, tetrabutylammonium fluoride, and tetraoctylammonium fluoride, especially tetrabutylammonium fluoride. Choice(s) of base will vary with the particular system of aryl halide or pseudohalide and silane involved.
Directly bonded to the aromatic ring(s) of the aryl halide or pseudohalide (i.e., aryl halide or aryl pseudohalide) is at least one halogen atom selected from a chlorine atom, a bromine atom, and an iodine atom, or at least one pseudohalide group. The term xe2x80x9cpseudohalide groupxe2x80x9d includes such groups as p-toluenesulfonate (tosylate), trifluoromethanesulfonate (triflate), methanesulfonate (mesylate), nonaflate (ONf), and aryl diazonium salts. (ArN2⊕X63, where X63  is halide, BF463, etc.). The aryl halide or pseudohalide can have two or more such halogen atoms with an atomic number greater than nine and/or pseudohalide groups, including combinations of halogen atoms and pseudohalide groups. However, when two or more such groups are present, the halogen atoms with an atomic number greater than nine and/or pseudohalide groups should all be different from each other. For example, when two such substituents are present, they may be a chlorine atom and a bromine atom, or an iodine atom and a tosylate group, or etc. It is preferred that there is only one chlorine atom, bromine atom, iodine atom, or pseudohalide group directly bound to the aryl ring of the aryl halide or pseudohalide. Aryl chlorides are more preferred as the aryl halide reactants. To prevent self-reaction, it is preferred that silyl groups are not present on the aryl halide or pseudohalide.
The aryl moiety for the aryl halide or pseudohalide can be homocyclic or heterocyclic. Examples of suitable homocyclic aryl moieties include, but are not limited to, benzene, naphthalene, anthracene, phenanthrene, pyrene, biphenyl, acenaphthalene, fluorene, and indene. Heterocyclic aryl moieties that can be used include, for example, furan, thiophene, pyridine, indole, oxathiolane, isoxazole, thianthrene, isobenzofuran, phenoxathiin, and the like. Benzene is a preferred aryl moiety for the aryl halide or pseudohalide.
For the aryl halide or pseudohalide, substituents other than a chlorine atom, a bromine atom, an iodine atom, and/or a pseudohalide group that may be present on the aromatic ring(s) include, but are not limited to, hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, ether groups, ketone groups, and ester groups. When hydrocarbyl groups are present, they are preferably C1 to C18 alkyl groups or C6 to C20 aryl or; aralkyl groups. Examples of suitable hydrocarbyl groups are methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl. Alkoxy group substituents preferably have C1 to C6 alkyl moieties. Some examples of alkoxy groups are methoxy, ethoxy, isopropoxy, methylcyclopentoxy, and cyclohexoxy. Perfluorohydrocarbyl groups include alkyl and aryl perfluorocarbons; suitable perfluorohydrocarbyl groups are, for example, trifluoromethyl, pentafluoroethyl, pentafluorophenyl, and heptafluoronaphthyl. The substituents preferred for the aryl halide or pseudohalide will depend on the product that is desired.
When an aryl moiety is the unsaturated group of the silane, the aryl moiety can be homocyclic or heterocyclic, as described for the aryl halide or pseudohalide. For the silane, the preferred aryl moieties are benzene and naphthalene. Substituents on the aryl ring, again as described for the aryl halide or pseudohalide, can be hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, ether groups, ketone groups, and ester groups. To prevent self-reaction, it is preferred that chlorine atoms, bromine atoms, iodine atoms, and/or pseudohalide groups are not present on aromatic ring(s) in the silane. In other words, the aryl moiety of the silane is preferably devoid of halogen atoms with an atomic number greater than nine, and preferably is also devoid of pseudohalide groups. However, one or more fluorine atoms can be present on the aromatic ring(s). Preferred unsaturated groups for the silane depend on the desired product.
The unsaturated group of the silane, when not an aryl moiety, may be a vinyl, allyl, alkenyl, benzyl, or aryloxy moiety. Suitable unsaturated groups are vinyl, allyl, benzyl, 1-butenyl, 1-cyclobutenyl, 2-pentenyl, cyclohexenyl, 1-hexenyl, 1-heptenyl, 2-octenyl, phenoxy, naphthoxy, biphenyloxy, phenanthroxy, fluorenoxy, and the like. A large variety of substituents, as described for the aryl moieties, can be present in the unsaturated group.
The saturated groups of the silane may be the same or different, and are preferably saturated hydrocarbyl or saturated hydrocarbyloxy groups. The saturated hydrocarbyl groups can be branched, straight chain, or cyclic. More preferred are hydrocarbyl groups containing from one to ten carbon atoms. Examples of suitable groups include, but are not limited to, methyl, ethyl, isopropyl, n-butyl, sec-butyl, 2-pentyl, cyclopentyl, methylcyclohexyl, heptyl, octyl, nonyl, and decyl. Much as described for the saturated hydrocarbyl groups, the hydrocarbyl portion of the saturated hydrocarbyloxy groups can be branched, straight chain, or cyclic. Similarly, hydrocarbyl portions of the saturated hydrocarbyloxy groups containing from one to ten carbon atoms are more preferred. Suitable saturated hydrocarbyloxy groups include methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, tert-butoxy, cyclobutoxy, 3-pentoxy, 4-methylcyclohexoxy, 4-heptoxy, 1-octoxy, 2-nonoxy, and 1-decoxy. Especially preferred saturated groups for the silane are methyl groups and methoxy groups; it is also preferred that all of the saturated groups are the same.
Silanes suitable for use in this invention include, but are not limited to, vinyltrimethylsilane,phenyl(trimethyl)silane,trimethyl(3-methylbenzyl)silane, (6-methoxy-2-naphthyl)trimethylsilane, triethyl(vinyl)silane, triethyl(pentafluorophenyl)silane, (allyl)tripropylsilane, tripropyl(o-tolyl)silane, tri-n-butyl(3-methyl-2-butenyl)silane, tri-n-butyl(vinyl)silane, vinyltrimethoxysilane, phenyltrimethoxysilane, (6-methoxy-2-naphthyl)trimethoxysilane, naphthyltriisopropoxysilane, phenyldimethoxyisopropoxysilane, phenoxytriisopropylsilane, naphthoxyethyldimethylsilane, (6-methoxy-2-naphthoxy)trimethoxysilane, and phenanthroxytrimethoxysilane.
The metal compound comprises at least one metal atom selected from nickel, palladium, and platinum having a formal oxidation state of zero or two, and is sometimes referred to hereinafter as the metal compound. Inorganic salts of nickel, palladium, or platinum that can be used include the bromides, chlorides, fluorides, iodides, cyanides, nitrates, sulfides, sulfites, and sulfates. Organic nickel, palladium, or platinum compounds that may be used include complexes and salts, such as the carboxylates, e.g., the acetates or propionates, etc. Suitable nickel compounds include bis(1,5-cyclooctadiene)nickel, nickel acetate, nickel oxalate, nickel phosphate, nickel stearate, nickel acetylacetonate, nickel tetrafluoroborate, nickel thiocyanate, nickel carbonate, and nickel sulfamate. Examples of palladium compounds include Pd(OAc)2, palladium(II) chloride, Pd(CH3CN)4(BF4)2, tris(dibenzylideneacetone)dipalladium(0) [which is also referred to herein as dipalladium tris(dibenzylideneacetone)], and palladium trifluoroacetate. Platinum compounds that can be used include platinum acetylacetonate and platinum chloride. Nickel and palladium compounds are preferred; more preferred are compounds of palladium. Palladium compounds such as palladium acetate and tris(dibenzylideneacetone)dipalladium(0) are most preferred.
Preferred types of N-heterocyclic carbenes are
A) imidazoline-2-ylidenes of the formula 
or protonated salts thereof, wherein at least R1 or R2 is an alkyl or aryl group having at least 3 carbon atoms, R3 and R4 are each, independently, a hydrogen atom, a halogen atom, or a hydrocarbyl group;
B) imidazolidine-2-ylidenes of the formula 
or protonated salts thereof, wherein R1, R2, R3, and R4 are as defined for the imidazoline-2-ylidenes;
C) bis(imidazoline-2-ylidene)s of the formula 
or protonated salts thereof, wherein R1, R2, R3, and R4 are as defined for the imidazoline-2-ylidenes, wherein R3xe2x80x2 and R4xe2x80x2 are as defined for R3 and R4 for the imidazoline-2-ylidenes, and wherein R5 is a bridging group that links the two imidazoline rings;
D) bis(imidazolidine-2-ylidene)s of the formula 
or protonated salts thereof, wherein R1, R2, R3, and R4 are as defined for the imidazoline-2-ylidenes, wherein R3xe2x80x2 and R4xe2x80x2 are as defined for R3 and R4 for the imidazoline-2-ylidenes, and wherein R5 is a bridging group that links the two imidazolidine rings.
It is preferred that both R1 and R2 are secondary or tertiary groups. More preferably, R1 and R2 are sterically bulky groups. Suitable groups include, but are not limited to, isopropyl, sec-butyl, tert-butyl, 2,2-dimethylpropyl (neopentyl), cyclohexyl, norbornyl, adamantyl, tolyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, and triphenylmethyl. Preferred groups are tert-butyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, and triphenylmethyl. Most preferred for both R1 and R2 are the 2,4,6-trimethylphenyl and 2,6-diisopropylphenyl groups.
Examples of suitable R3, R4, R3xe2x80x2, and R4xe2x80x2 groups include chlorine atoms, bromine atoms, hydrogen atoms, hydrocarbyl groups, and the like. When hydrocarbyl groups are present, they are preferably C1 to C18 alkyl groups or C6 to C20 aryl or aralkyl groups. Examples of suitable hydrocarbyl groups are methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl. Chlorine atoms and hydrogen atoms are preferred groups. Most preferred for all substituents R3, R4, R3xe2x80x2, and R4xe2x80x2 are hydrogen atoms.
R5 in both the formula for the bis(imidazoline-2-ylidene)s and the bis(imidazolidine-2-ylidene)s of this invention can be selected from a large variety of moieties, including alkylene groups, arylene groups, and silylene groups. Atoms that can form the bridge include, but are not limited to, carbon, nitrogen, oxygen, silicon, and sulfur. Examples of suitable bridging moieties include methylene (xe2x80x94CH2xe2x80x94), substituted methylene, ethylene (xe2x80x94CH2CH2xe2x80x94), substituted ethylene, silylene ( greater than SiR2), benzo (C6H4 less than ), substituted benzo, biphenylene, substituted biphenylene, binaphthylene, and substituted binaphthylene. Heterocyclic aromatic moieties such as, for example, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, oxathiolane, thianthrene, isobenzofuran, phenoxathiin, isothiazole, phenoxazine, and the like, can also form the bridge. Preferred R5 moieties include biphenylene, binaphthylene, and substituted benzo, with substituted benzo being more preferred. Highly preferred is benzo substituted with methyl groups. The bridge preferably has at least four atoms, and more preferably has from four to eight atoms. While better results have been observed with longer bridges, it is possible that judicious choices for R1, R2, R3, R4, R3xe2x80x2, and R4xe2x80x2 may improve results for short bridges.
Without being bound by theory, it appears from thermochemical studies that the electron-donating ability of many of the imidazoline-2-ylidene carbene ligands is better than that of tri(cyclohexyl)phosphine and the steric demand of these carbene ligands is greater than that of tri(cyclohexyl)phosphine. This suggests that the N-heterocyclic carbene should possess steric bulk sufficient to stabilize both the free carbene and to stabilize reaction intermediates. However, imidazoline-2-ylidene carbenes and imidazolidine-2-ylidene carbenes are considerably less stable to air and moisture than their corresponding protonated imidazolinium and imidazolidinium salts. Thus, a highly preferred embodiment of this invention involves generation of the imidazoline-2-ylidene in situ from the corresponding imidazolinium salt (similarly so for the imidazolidine-2-ylidene and the corresponding imidazolidinium salt); this removes the need to handle the N-heterocyclic carbene ligands in an inert atmosphere. Protonated salts of the imidazoline-2-ylidene carbenes and imidazolidine-2-ylidene carbenes are monoprotonated, while the protonated salts of the bis(imidazoline-2-ylidene)s and the bis(imidazolidine-2-ylidene)s are diprotonated. Suitable counterions for the protonated salts are virtually limitless, but halides are preferred counterions. The most preferred counterions are chloride and bromide. The imidazolinium salts are straightforward to synthesize and are air-stable. While the absence of oxygen is not necessary when using a protonated salt of an imidazoline-2-ylidene carbene or an imidazolidine-2-ylidene carbene, it is preferred. When using a neutral carbene, the absence of oxygen is necessary. In any instance where oxygen is excluded, the presence of an inert gas such as nitrogen, helium, or argon is preferred.
The aryl halide or pseudohalide and the silane may be employed in an ideal molar ratio of about 1:1 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group; or either reagent may be used in excess. It is preferred to use the silane in an excess such that the molar ratio of aryl halide or pseudohalide to silane is in the range of from about 1:1.5 to about 1:4 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group. When the aryl halide or pseudohalide has more than one halogen atom (other than fluorine) and/or pseudohalide group, reactions may be carried out in sequence. A silane will react first at the site of the more reactive substituent, e.g., at iodine before bromine. Reaction at only the site of the more reactive substituent(s) can be performed. In reactions carried out in sequence where the silanes are different, each should be added separately. It is preferred to allow one reaction to finish before the addition of the next silane. When different silanes are used, it is preferred to use close to the ideal molar ratio of aryl halide or pseudohalide to silane to minimize undesirable side products.
A suitable molar ratio of aryl halide or pseudohalide to strong base is in the range of from about 1:1 to about 1:5. A more preferred molar ratio of aryl halide or pseudohalide to strong base is in the range of from about 1:1 to about 1:3.
Normally, the molar ratio of metal atoms of the metal compound to aryl halide or pseudohalide molecules is in the range of from about 0.01:1 to about 0.05:1; a preferred molar ratio of metal atoms of metal compound to aryl halide or pseudohalide molecules is in the range of from about 0.02:1 to about 0.04:1. For the metal compound and the carbene ligands, the molar ratio of metal atoms of the metal compound to carbene molecules is in the range of from about 1:0.5 to about 1:5, and more preferably in the range of from about 1:1 to about 1:3.
The order of addition of the various components to a reaction vessel is not of particular importance. Premixing of the components of the catalyst system is not necessary; however, it is preferred that the catalyst system is premixed. To premix the components of the catalyst system, the metal compound, the N-heterocyclic carbene (salt or neutral compound), and the strong base are mixed together after being added in no particular order to a reaction vessel. The mixing time (activation period) for these components on the laboratory scale may be very short, e.g., five minutes or less, but a preferred mixing time is in the range of from about fifteen minutes to about sixty minutes.
If a premixed catalyst system is used, the aryl halide or pseudohalide and the silane may be added to the same reaction vessel, or the premixed catalyst system can be transferred to a different vessel in which the reaction is to take place. Use of the same vessel for premixing the catalyst system and conducting the reaction is preferred.
When the components of the catalyst system are not premixed, the strong base, aryl halide or pseudohalide, the silane, the metal compound, the liquid medium, and the N-heterocyclic carbene (salt or neutral compound) are added in any order to the reaction vessel.
Once all of the components are present in the same reaction vessel, the mixture may be heated, provided that the temperature does not exceed the thermal decomposition temperature of the catalyst system or the products of the reaction. Preferred temperatures are in the range of from about 20xc2x0 C. to about 150xc2x0 C.; more preferred temperatures are in the range of from about 20xc2x0 C. to about 110xc2x0 C. When the aryl halide or pseudohalide is an aryl chloride, an aryl triflate, or an aryl tosylate, heat is usually necessary to drive the reaction. Preferred temperatures when the aryl halide or pseudohalide is an aryl chloride, an aryl triflate, or an aryl tosylate are in the range of from about 40xc2x0 C. to about 150xc2x0 C. When the aryl halide or pseudohalide is an aryl bromide or an aryl iodide, the reaction(s) usually proceeds at room temperature, although heat may speed the reaction. For aryl bromides and aryl iodides, preferred temperatures are in the range of from about 20xc2x0 C. to about 90xc2x0 C.
Occasionally, a small amount of homocoupled product is observed. Use of a lower reaction temperature and a larger amount of silane usually decreases the quantity of homo-coupling product obtained, thus increasing the yield of the desired heterocoupled product.
While not necessary when using protonated salts of N-heterocyclic carbenes, the absence of oxygen and water is preferred when conducting the processes of this invention. Conversely, the exclusion of oxygen and water is generally necessary when neutral carbenes are used. The presence of an inert gas such as argon or nitrogen is preferred when oxygen and/or water are excluded. The reaction mixture is normally agitated. A preferred contact time for the components of the reaction is in the range of from about one hour to about forty-eight hours. More preferably, the contact time is from about one hour to about twenty-four hours.
The following examples are presented for purposes of illustration, and are not intended to impose limitations on the scope of this invention.